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Prevalence of thiopurine S-methyltransferase gene polymorphisms in patients with inflammatory bowel disease from the island of Crete, Greece

Coucoutsi, Constantinaa,c; Emmanouil, Georgea; Goulielmos, Georgeb; Sfakianaki, Ouraniaa; Koutroubakis, Ioannis E.c; Kouroumalis, Elias A.a,c

European Journal of Gastroenterology & Hepatology: November 2017 - Volume 29 - Issue 11 - p 1284–1289
doi: 10.1097/MEG.0000000000000947
Original Articles: Inflammatory Bowel Disease

Background There is evidence that genotyping for the thiopurine S-methyltransferase (TPMT) gene variants is useful for the prediction of response to thiopurine analogs (azathioprine and 6-mercaptopurine) in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of TPMT gene polymorphisms in a genetic homogenous population of IBD patients in Crete and to correlate the results with adverse reactions to thiopurine drugs.

Patients and methods Genotyping for the most common TPMT variants TPMT*2, TPMT*3A, TPMT3*C, and TPMT*3B was performed using the PCR-restriction fragment length polymorphism method in 223 consecutive IBD patients and 119 age-matched and sex-matched healthy controls. The hospital medical records were reviewed for thiopurine use in these patients and related adverse events.

Results The prevalence of TPMT variants TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C was 1.8, 2.7, 1.3, and 1.8%, respectively. The G238C mutation was detected in four (1.8%) out of 223 patients, three (1.3%) patients were carriers of the G460A mutation, four (1.8%) of the A719G mutation, and six (2.7%) of both G460A and A719G mutations. In healthy controls, only one (0.8%) carried both the G460A and the A719G mutation, whereas TPMT*2, TPMT*3C, and TPMT*3B were not detected. None of the genotypes was homozygous. A statistically significant correlation between the presence of the G460A mutation and the development of leucopenia after the administration of thiopurines was observed (P=0.048).

Conclusion This study showed a lower frequency of total TPMT variants and a higher frequency of TPMT*3B in Cretan IBD patients compared with other Caucasian populations. The presence of the G460A mutation is associated with the development of leukopenia.

aLaboratory of Gastroenterology

bSection of Molecular Pathology and Human Genetics, Faculty of Medicine, University of Crete

cDepartment of Gastroenterology, University Hospital of Heralion, Crete, Greece

Correspondence to Constantina Coucoutsi, MD, Laboratory of Gastroenterology, Faculty of Internal Medicine, University of Crete, Voutes, 71003 Crete, Greece Tel: +30 697 799 1042; fax: +30 289 102 5099; e-mail:

Received March 29, 2017

Accepted May 23, 2017

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.